The broad purpose of this work is to further understand how microorganisms and vaccine adjuvants via their interaction with antigen presenting cells, such as macrophages and dendritic cells, affect the generation of T cell mediated immune responses via their ability to regulate the production of critical cytokines, such as IL-12 and IL-10, and type-1 interferons. Over the past year, we have focused on the genetic determinants for the regulation of cytokine production in mouse models of colitis. WE have also developed a new model of autoimmune eye disease that is mediated by similar genetic determinants as colitis induction. We have also been exploring ways to exploit signaling pathways that negatively regulate IL-12 and IL-23 production for the suppression of autoimmune disease. Several years ago we identified that signaling though another surface receptor, complement-receptor 3 (CD3,CD11b/CD18, Mac-1) inhibits IL-12 but not IL-10 production by human monocytes, and that antibodies to CR3 could be used to suppress IL-12 production in vitro. This has implications for understanding how pathogens that use CR3 as an receptor for entry into cells like monocytes and macrophages, have explited this pathway by preventing adequate IL-12 and Th1 responses necessary for their rapid erradication. In addition, they suggested that anti-CR3 may be used to inhibit abnormal inflammatory diseases. Preveiously we evaluated the ability of antibodies to CR3 to treat murine models of colitis and skin inflammation. We determined that anti-CR3 could be used effectively to treat inflammatory colitis and psorisiform dermatitis, indicating a possible novel approach to treatment of inflammatory bowel disease and psoriasis in humans. Over the past year, we have begun testing anti-CR3, as well as anti-IL-12p40 to treat a novel model of autoimmune keratoconjuctivitis that is similar to what occurs in dry-eye disease in humans.